Presentation: Fetus that is small for gestational age

A woman attends her 28-week community midwife appointment and is found to have a symphysis fundal height below the 10th centile on her customised growth chart. She is referred to secondary care for a fetal growth scan, at which it is confirmed that the fetus is on the first centile based on fetal biometry.

• Genomic testing should be discussed in cases in which there is significant growth restriction with no evidence of placental insufficiency or other suspected cause.
  • There is still a possibility of placental insufficiency and a co-existent genomic cause for small fetal size.
• Genomic testing should be discussed in cases in which small-for-gestational-age (SGA) is present alongside other fetal anomalies, or in which early pregnancy aneuploidy screening returned a higher chance result.

• Consult the National Genomic Test Directory. From this directory you can access the rare and inherited disease eligibility criteria for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
  • For those working within NHS Wales, please consult the All Wales Medical Genomics Service website for information on how to arrange testing.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Refer to local guidance regarding fetal medicine referral as further review in a fetal medicine unit is usually warranted.
• The fetal medicine review will determine whether genomic testing is appropriate, and referral to clinical genetics will be considered. Referral to clinical genetics is not routinely indicated unless fetal exome sequencing is planned (see below).
• The fetal medicine team will decide which testing is most suitable for the patient and/or discuss the case with a multidisciplinary team, depending on the specific clinical scenario and the patient’s wishes.
• Depending on the clinical scenario, a range of different genomic tests may be considered:
  • R22 Fetus with a likely chromosomal abnormality. This will process both:
    • R22.1 Genome-wide common aneuploidy testing; and
    • R22.2 Chromosomal microarray.
  • R21 Fetal anomalies with a likely genetic cause: fetal exome sequencing can be considered under the following circumstances:
    • All measurements <third percentile (including abdominal circumference and head circumference) with a confirmed early ultrasound estimated date of delivery scan; and
      • no evidence of placental insufficiency including normal fetal and maternal dopplers;
      • no history of previous fetal growth restriction or stillbirth;
      • normal PAPP-A (if measured); and
      • no maternal history of systemic lupus erythematosus (SLE) or similar.
    • Referral to clinical genetics and/or multi-disciplinary discussion is required.
  • Where a specific genetic condition is considered likely or there is a relevant family history, further guided genomic testing my be recommended.
• For tests that are undertaken using whole genome sequencing (WGS), you will need to:
  • complete an NHS GMS test order form with details of the proband and parents. Include details of the phenotype (refer to human phenotype ontology (HPO) terms or the clinical summary) and the appropriate panel name(s) with associated R number (see How to complete a test order form for WGS for support).
  • complete an NHS GMS ROD form for each person being tested. Note that, if you are undertaking trio testing of an affected child and their parents, you will need three of these forms. (see How to complete a record of discussion form for support).
  • parental samples should be submitted alongside the child’s sample. This is called trio testing. If this is not possible, such as when testing a child in care or a parent is unavailable for testing, the child may be tested as a singleton.
• For tests that do not include WGS, you will need to:
  • complete a test order form and consent (record of discussion) form, available from your local Genomic Laboratory Hub (GLH).
  • include details of the phenotype in the test order form (refer to HPO terms or the clinical summary) as well as the appropriate panel name(s) with associated R number.
  • parental samples may be needed for interpretation of the proband’s result. Parental samples can be taken alongside that of the proband, and their DNA stored, or can be requested at a later date if needed.
• All of the above tests are DNA based and require an amniocentesis or chorionic villus sample or fetal blood sample in an EDTA tube (purple-topped tube).
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• NHS England: National Genomic Test Directory
• Royal College of Obstetricians and Gynaecologists: Small-for-gestational-age fetus, investigation and management (Green-top Guideline No. 31)

For patients

• Royal College of Obstetricians and Gynaecologists: Having a small baby